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Biomedical subjects

H Davies

Publications and source records attributed to H Davies.

At least 91 records · Page 5Linked to original sources

An analysis of paediatric diagnostic decision-making: how should students be taught?

This study assesses the relative importance of history, examination and investigations in paediatric diagnosis, in the Paediatric Out-patient Department of the Central Middlesex Hospital, London, by means of a questionnaire-based record of 94 consecutive referrals. A diagnosis identical to the final diagnosis was made in 76% of referrals after taking a history. The general practitioner had proposed a diagnosis in 45% in the referral letter. Clinical examination changed the diagnosis in only 15% but increased diagnostic confidence in 33%. Ninety-one per cent of cases were diagnosed without recourse to investigations. Forty-two per cent of children referred had investigations performed. In the majority of paediatric cases the provisional diagnosis reached after taking a history was identical to that after examination or results of investigations were known. Although examination provided a final diagnosis in only 15% of all cases it played an important role in adding confidence in 33%. More educational effort should therefore be directed at clinical history-taking skills and the subsequent purpose of examination.

Clinical Competence↗

Can dynamic krypton-81m imaging separate regional ventilation and volume?

This study explores the assumption that 81mKr static images represent regional ventilation. Dynamic acquisition of 81mKr ventilation images permits creation of time-activity curves and the possible separation of the confounding influences of ventilation and volume. By using a two-compartment gas mixing lung phantom, the results demonstrate that both total and tidal 81mKr are closely related to regional ventilation. In 61 children and 15 adult volunteers, there was good agreement between fractional ventilation assessed by total and tidal 81mKr. The dynamic steady-state ventilation image can be analyzed to separate tidally exchanged and resident 81mKr. This may allow regional ventilation to be distinguished from regional volume.

Adolescent↗

Adenine photodimerization in deoxyadenylate sequences: elucidation of the mechanism through structural studies of a major d(ApA) photoproduct.

The mechanism of the photodimerization of adjacent adenine bases on the same strand of DNA has been elucidated by determining the structure of one of the two major photoproducts that are formed by UV irradiation of the deoxydinucleoside monophosphate d(ApA). The photoproduct, denoted d(ApA)*, corresponds to a species of adenine photodimer first described by Pörschke (Pörschke, D. (1973) J.Am.Chem.Soc. 95, 8440-8446). From a detailed examination of its chemical and spectroscopic properties, including comparisons with the model compound N-cyano-N1-(1-methylimidazol-5-yl)formamidine, it is deduced that d(ApA)* contains a deoxyadenosine unit covalently linked through its C(8) position to C(4) of an imidazole N(1) deoxyribonucleoside moiety bearing an N-cyanoformamidino substituent at C(5). On treatment with acid, d(ApA)* is degraded with high specificity to 8-(5-amino-imidazol-4-yl)adenine whose identity has been confirmed by independent chemical synthesis. It is concluded that the primary event in adenine photodimerization entails photoaddition of the N(7)-C(8) double bond of the 5'-adenine across the C(6) and C(5) positions of the 3'-adenine. The azetidine species thus generated acts as a common precursor to both types of d(ApA) photoproduct which are formed from it by competing modes of azetidine ring fission.

Adenine↗

The induction of cytotoxic T-lymphocyte precursor cells by recombinant vaccinia virus expressing human papillomavirus type 16 L1.

Expression of the major coat protein L1 of human papillomavirus type 16 by recombinant vaccinia viruses using a vaccinia late promoter and their use in generating antibodies have already been reported (Zhou et al., 1990). We have now constructed recombinant vaccinia viruses (VVs) which express the L1 protein from an early promoter with the intention of inducing cell-mediated immunity. This necessitated the removal of sequence motifs (TTTTTNT) from the L1 gene which would otherwise have caused transcription termination when expressed from a vaccinia virus early promoter. The nucleotide sequence was mutated to retain the correct amino acid sequence of the L1 protein. Full-length mRNA and L1 protein were generated in cells infected with the recombinant virus containing the mutant sequence, whereas the wild-type sequence generated only truncated mRNA and no detectable protein. Mice were immunized with VV expressing L1 from the mutant sequence and from the wild-type sequence in constructs with either early or late vaccinia virus promoters. Only the early promoter constructs were effective in priming cytotoxic T lymphocytes (CTL). Moreover the mutant sequence was significantly more effective than the wild-type sequence. The same L1 sequences, expressed from a vaccinia virus late promoter or coexpressed with MHC Class I molecules also expressed from a late promoter, produced high levels of L1 protein in both cases but nevertheless failed to elicit CTL activity. This is the first report of an HPV-specific CTL response and we have reaffirmed the importance of choosing the correct promoter and sequence expressed when using recombinant vaccinia viruses to induce cytotoxic T lymphocytes. These data are relevant for the design of vaccines to generate cell-mediated immunity against human papillomavirus infection.

Animals↗

The coronary arteries of the transplanted human heart: studies of the development of disease based on serial angiography.

291 coronary angiograms were performed routinely 1 to 8 years after cardiac transplantation in 116 patients operated on at Papworth Hospital between January 1979 and September 1986. In this setting, as in others, angiography tends to underestimate the amount of disease present, and the patterns of angiographic abnormality are various. The actuarial probability of freedom from angiographic evidence of coronary occlusion is 79% at 2 years, 76% at 3 years, 60% at 4 years, 57% at 5 years. We have defined two disparate groups designated 'fast disease' and 'slow disease', being respectively those who have angiographic and/or pathologic evidence of disease at two years, and those who have normal coronary angiograms at 5 years. In comparing features of these two groups, donor age, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglyceride level differ, though significantly only for the high density fraction.

Adult↗

Three wall orbital decompression for Graves' ophthalmopathy via a coronal approach.

Ten patients with dysthyroid eye disease who underwent a three wall orbital decompression procedure performed via a coronal approach were reviewed. The indications, results, complications and surgical techniques involved in this surgery are discussed. We believe that this approach offers a number of advantages over other techniques and has a role in the management of carefully selected patients with dysthyroid eye disease who have severe unilateral or bilateral proptosis, with or without dysthyroid optic neuropathy.

Adult↗

Cytogenetic studies of leukemic recurrence in recipients of bone marrow allografts.

Cytogenetic studies were made in 20 leukemic patients who relapsed after treatment by allogeneic bone marrow transplantation (BMT). Seven of the eight patients in whom no chromosomal abnormalities were detected in leukemic cells before BMT developed clonal abnormalities after BMT, and in two of these patients two independent clones were observed. Most patients in whom clones were detected before BMT showed evidence of clonal evolution after BMT. Nonclonal abnormalities were also observed in clonal cells. These additional abnormalities, both clonal and nonclonal, were attributed to the effects of total body irradiation received by the patient before BMT. There was no evidence of recurrence of leukemia in donor cells among these patients. We concluded that the cells found in leukemic recurrence were derived from the original leukemic clone.

Adolescent↗

Atherogenesis and the coronary arteries of childhood.

The coronary arterial intima undergoes a sequence of changes following injury, before the appearance of lipids. Studies of the evolution of coronary arterial pathology in the transplanted human heart defines a pattern which is the stereotype of the artery's response to insult. The first stage is that of intimal hyperplasia and disruption of the internal elastic lamina; the second the migration into the thickened intima of medial smooth muscle cells; the third the incursion of lipids. The end result is atheroma, indistinguishable morphologically from that which is found in the usual setting. The same sequence of arterial events can be sought, and found, in the general population (at least in coronary-prone societies), the first being identifiable commonly in infancy and childhood. These changes, reported in the literature over many years, have been generally assumed to be benign accompaniments of growth and development. They are likely to be the precursors of atherosclerosis and the seat of later lipid deposition, without which that deposition would not occur. The cause(s) of coronary arterial disease are therefore concerned more with these pre-lipid stages than with the lipids themselves, which are complicating rather than causative factors.

Animals↗

Developing collaborative research between clinical agencies: a consortium approach.

Collaborative research is receiving increased attention because it maximizes scarce resources and can increase research productivity. One form of collaboration, the consortium approach, was used by six hospitals in northern California and Nevada to increase research activity among the agencies. Our experience with this consortium approach is described. Advantages and disadvantages of this approach to facilitate collaborative research are presented. This approach is recommended for clinical agencies in geographic proximity with similar clinical concerns and administrators supportive of research activity.

Humans↗

Long term follow up after inhalation of foreign bodies.

The long term results of treatment of inhalation of foreign bodies in a district children's hospital and in a tertiary referral centre were reviewed by clinical assessment, chest radiography, and standard four view 81mKr ventilation/99mTc macroaggregated albumin perfusion imaging (V/Q lung scan). The overall incidence in the population served by the district hospital was roughly one in 14,000/year. Of the 12 children reviewed there, three had abnormal chest radiographs and four had abnormal V/Q scans as a result of inhalation of the foreign bodies. Of 21 children treated and reviewed at the referral centre, eight had abnormal chest radiographs, and 14 had abnormal V/Q lung scans. Three factors were assessed for prognostic importance: site of impaction, initial radiographic appearance, and time before removal. A child who had inhaled a foreign body into the left lung and who had collapse/consolidation on the initial chest radiograph was at greatest risk of long term complications. These children merit close follow up.

Child, Preschool↗

Phosphoinositides and plant growth substance action.

Synergism between 0.5 mM inositol and cytokinin in the stimulation of plant tissue culture growth suggests a role for inositol in the mediation of cytokinin action. Investigation of the effects of cytokinin on the pattern of labelling of lipids from radioactive precursors by cytokinin-responsive cells of a cytokinin-dependent soybean cell suspension culture did not detect any reproducible link between cytokinin action and lipid labelling after 10 min. Evidence for links between auxin action and phosphoinositide metabolism in other systems would benefit from confirmation of long term repeatability and more rigorous chemical characterization of the compounds involved. For plant growth substance action to be mediated by release of inositol trisphosphate from phosphatidylinositol bisphosphate, activation of phospholipase C, possibly requiring potentiation by a GTP-binding protein, would be expected. Reports of G-protein effects on plant phospholipase C activity are conflicting. There is evidence for G-protein stimulation of activity from the results of assays using endogenous substrates, although the products released have not been fully characterized. Other results, from assays using exogenous substrates, have shown no effect of GTP analogues on the enzymic breakdown of phosphatidylinositol bisphosphate. Using endogenously labelled membranes from soybean cells, we were unable to detect effects attributable to G-protein potentiation. None of a range of growth substances at physiologically active concentrations proved able to alter detectably the lack of response of polyphosphoinositidase activity to GTP-analogues. The activity was, however, strongly stimulated by Ca2+ at micromolar levels, a characteristic widely reported. In consequence, the possibility that transient increases in the labelling of inositol phosphate fractions may be a result of increases in cytosolic Ca2+ levels needs to be addressed. If there is a role for inositol in soybean cell activation by cytokinin, we have no evidence that it involves polyphosphoinositide cleavage. That there is a special role for inositol in the mitotic cycle of soybean cells and in addition to the maintenance of viability is shown by the results of experiments in which endogenous inositol synthesis was inhibited. Further research aims to identify the inositol-requiring steps and their relationship, if any, with the auxin-requiring and cytokinin-requiring steps in the mitotic cycle of cultured soybean cells.

Cell Division↗

Examination of submandibular fluid in cystic fibrosis.

A novel collecting device was used to obtain pure submandibular saliva from control and Cystic Fibrosis (CF) individuals. Vitamin C stimulation induced a 2-fold increase in flow rate relative to resting; CF rates were lower under both conditions. Control and CF saliva differed in that stimulation did not result in increased Na+ and Cl- levels in CF saliva and that elevated levels of Ca2+ and PO4(2-) were observed in CF. The results imply altered electrolyte secretion in CF in response to a stimulus in vivo.

Adult↗

REM latency in Alzheimer's disease.

Latency to the first episode of rapid eye movement sleep (REML) has been proposed as a potential biomarker for Alzheimer's disease (AD). In this study, we compared REML values from 28 AD patients and 28 age- and sex-matched controls. We employed multiple definitions of REML and multiple cutoffs to classify patients and controls. Results indicated that the best REML definition and optimal cutoff criterion resulted in only 65% correct classifications. We discuss the longer REML in AD patients relative to controls in terms of both overall sleep disturbance and selective deterioration of the REM-cholinergic system. As REML may be relatively short in other forms of psychopathology (e.g., affective disorders), REML may still hold promise in the differential diagnosis of dementia and pseudodementia.

Aged↗

Coronary arterial pathology in the transplanted human heart.

The coronary arteries of 23 transplanted human hearts have been studied following death or re-transplantation, 8 days to 8 years after surgery, with a view to defining the sequence of changes in the first months. Occlusive arteritis occurs in association with acute rejection. Intimal hyperplasia, usually accompanied by disruption of the internal elastic lamina and proliferation of smooth muscle cells, may be seen within two weeks. Lipids and mucopolysaccharides appear in the thickened intima only after about 2 months. The end-state of the process is atherosclerosis, indistinguishable from that of the non-transplanted heart: for this to occur the patient must survive long enough, and therefore the early coronary occlusive process must not be too vigorous. It is unlikely that there are two different diseases of the transplanted coronaries, "chronic rejection" and "atherosclerosis". The apparent difference between these is due to the absence or presence of lipid, which is a function of time. In the transplanted heart, lipid is not an inciting factor in the arteriopathy. In this, the role of mitogens would appear to be critical.

Adult↗